Báo cáo y học: "Understanding the cognitive consequences of critical illness through experimental animal models" pps

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Available online />Abstract
Tuon and colleagues have developed an animal model to examine
the impact of sepsis on memory in rats. They report important data
that expand the understanding of the cognitive consequences of
critical illness. Future research should follow this path of inquiry
and extend animal models beyond aversive conditioning to include
recently developed paradigms that will permit assessment of
complex and cognitive processes, such as attention, episodic
memory and orientation to time and place. This has the potential to
greatly increase the putative understanding of the homologous
neurocognitive dysfunctions acquired during critical illness.
Major progress has been made over the past 20 years in the
understanding of the cognitive consequences of critical
illness. In order to expand the knowledge how disease states
such as sepsis have a causal impact on the central nervous
system and cognition, experimental animal models are
certainly required. In a previous issue of Critical Care, Tuon
and colleagues [1] reported a study in which they developed
such a model in order to simulate the cognitive and
behavioral effects of septic illness on memory functioning.
They further provide evidence that this memory impairment
can be attenuated by the administration adrenergic agents,
which suggests that this mnemonic pathway may be
mediated by adrenoceptors.
The methodology employed by Tuon and colleagues [1] has
been used in behavioral neuroscience and comparative
psychology since the inception of classical conditioning [2,3].
It is a well validated methodology that elicits a clear link
between stimulus encoding and behavioral output. Other

recent research has provided important insights into the
nature of aversive memory formation. As the understanding of
memory and other cognitive processes has expanded, so too
have the ties between these cognitive functions and the
underlying anatomy and physiology supporting these abilities.
Elegant studies have revealed that memory is a complex
construct indeed. Memory is a multifaceted ability that is
supported by disparate and distinct circuits in the brain, so
much so that ablating structures in one mnemonic pathway
may have little or no effect on the functioning of another
mnemonic ability. In the classic neuropsychological evaluation
of patient ‘HM’, even with profound anterograde amnesia that
developed after removal of a major section of the medial
temporal lobe, he was still able to form classically conditioned
memories, specifically to aversive events [4,5].
In recent years several methodologies have been developed
that extend the ability to address questions regarding
complex cognitive processes in animal models. For example,
Jonathan Crystal at the University of Georgia has demon-
strated that it is possible to test not only episodic memory in
animals but also attention and orientation to time and place
[6,7]. Although each of these abilities involves a component of
memory, these cognitive faculties differ in important ways from
aversive classical conditioning. Not only do these mnemonic
processes rely on fundamentally different neurological
substrates, but they are also homologous to the memory and
attentional deficits that are observed in survivors of critical
illness. By incorporating paradigms such as those developed
by Crystal and colleagues, future animal models have the
potential to answer important questions regarding the nature

of higher level cognitive deficits experienced by patients who
survive critical illness in the intensive care unit (ICU). It may
then be possible to begin to trace specific circuits related to
ICU-acquired neurocognitive injury. This could lead to an
improved understanding of the sometimes subtle nature of
attentional, declarative, and executive dysfunction observed in
patients after critical illness. Increasingly sophisticated animal
Commentary
Understanding the cognitive consequences of critical illness
through experimental animal models
Max L Gunther
1
and Brett English
2
1
Department of Radiological Sciences, Center for Health Services Research, Vanderbilt University Medical Center, Vanderbilt Institute of Imaging
Sciences, Nashville, TN 37232-8300, USA
2
Department of Pharmacology, Center for Molecular Neuroscience, 465 21st Ave South, 7150 MRB III, Nashville, TN. 37232-8548, USA
Corresponding author: Max L Gunther,
Published: 8 January 2009 Critical Care 2009, 13:104 (doi:10.1186/cc7126)
This article is online at />© 2009 BioMed Central Ltd
See related research by Tuon et al., />ICU = intensive care unit.
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Critical Care Vol 13 No 1 Gunther and English
models of higher level cognition and behavior are being
developed. The hope is that these may help bridge the gap
between bench research and bedside care. Experimental
investigations that incorporate the ability to assess subtle

changes in animal cognition offer great promise for
advancing our understanding ICU acquired long-term
cognitive impairment.
Competing interests
The author declares that they have no competing interests.
References
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